Combined autologous bone marrow mononuclear cell and gene therapy as the last resort for patients with critical limb ischemia

Abstract

IntroductionOur study was designed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell (MNC) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia (CLI).Material and methodsThirty-two patients with CLI persisting for 12–48 months (average time 27.5 months) were randomized into 2 groups, each group consisting of 16 patients. In the first group, administration of autologous bone marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed. The patients from the second group were treated pharmacologically with pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was performed before and finally 3 months after treatment. The pain was evaluated using the Visual Analog Scale (VAS) before and after 3 months.ResultsAnkle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 (p < 0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1. In this group angiography showed the development of collateral vessels. Ischemic ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not improve in any patient; moreover the complete healing of skin ulcers was not found in any of the patients of this group. Amputation was performed in 4 (25.0%) patients in group 1, and in 8 patients (50%) from group 2.ConclusionsThese data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe, and a more feasible and effective method of treatment than the conventional therapy. However, both therapies are limited by the degree of microcirculation damage.

Functions of the AP-2α gene in activating apoptosis and inhibiting proliferation of gastric cancer cells both in vitro and in vivo

“…Thus, it is crucial to choose an appropriate target therapy gene such that the effects of gene therapy are limited to cancer cells. Recently, several preliminary studies of targeted genes in gastric cancer have been performed [ 8 , 9 ].…”

Peripheral arterial disease: Scoping review of patient‐centred outcomes

“…Reduced levels or incidence of amputations were also reported in seven studies on 164 patients treated with autologous stem cells 63,77,[101][102][103][104][105] ; seven studies on 294 patients receiving spinal cord electrical stimulation [81][82][83][106][107][108][109] ; four studies on 764 patients receiving ER 27, 60,110,111 ; two studies on 107 patients treated with systemic prostanoids 84,112 ; two studies on 80 patients treated with growth factors within a meta-analysis 30 ; and one study on 24 patients receiving IPC. 91 One study reported improved amputation outcomes for 106 individuals with mild-to-moderate PAD who received ER with SET.…”

Therapeutic efficacy of CD34+ cell-involved mononuclear cell therapy for no-option critical limb ischemia: A meta-analysis of randomized controlled clinical trials

“…A total of 11 RCTs were included in the qualitative analysis. [26][27][28][29][30][31][32][33][34][35][36] Tateishi-Yuyama et al's trial was excluded from quantitative synthesis due to its inappropriate placebo administration using PB-MNCs with low CD34 expression. 26 Skóra et al's trial was also excluded because its intervention of BM-MNCs plus vascular endothelial growth factor (VEGF) 165 DNA plasmid intramuscular injection was not limited to cell therapy.…”

“…26 Skóra et al's trial was also excluded because its intervention of BM-MNCs plus vascular endothelial growth factor (VEGF) 165 DNA plasmid intramuscular injection was not limited to cell therapy. 35 All the included trials were designed as two-armed except that Losordo et al 32 reported a dose-escalation three-armed trial, in which the low-dose and the high-dose CD34 + cell intervention group were independent of each other, sharing the same placebo group. Therefore, nine RCTs (10 studies) were ultimately quantitatively analyzed, wherein the two dosage groups with equally divided control groups of Losordo et al's trial were separated into two studies.…”